1. Field of the Invention
The present invention relates to a device for transporting, trapping and escaping biomaterial using micro-magnetophoretic circuit and magnetic structures, and a method for transporting, trapping and escaping biomaterial using the same.
2. Description of the Related Art
It is difficult for existing laboratory systems to promptly process a large amount of bio-information poured as the human genome project has been completed and the post-genomic era has arrived. Accordingly, biological identification systems for investigation of vital phenomena, development of new drug and diagnosis are being developed into the forms of a micro-Total Analysis System (μ-TAS) and a lab-on-a-chip, which are for analyzing a sample accurately and conveniently in a short time with less amount of the sample on the basis of microfluidics.
Since most of biochemical samples to be analyzed area present in the form of a solution, a technique to translocate the liquid sample can be the most important factor. The microfluidics is just the field of microfluidic flow control, and is the field of studying and developing essential technologies that form the foundation of commercialization of the μ-TAS and the lab-on-a-chip.
The μ-TAS is a system that totally carries out chemical and biological experiment and analysis, which go through a plurality of experimental steps and reactions, on a single unit present in a single experimental stand. This μ-TAS includes a sample collection area, a microfluidic circuit, a detector and a controller for controlling them.
Meanwhile, the lab-on-a-chip means a laboratory within a chip or a laboratory on a chip, in which a microfluidic channel of nanoliter or smaller is fabricated using a material such as plastic, glass and silicon and a liquid sample of only several nanoliters is translocated through the microfluidic channel, whereby existing experimental or study procedures can be carried out quickly.
Realization of μ-TAS or a lab-on-a-chip capable of quickly carrying out analysis for sharply increasing bio-information can be effectively achieved when it is combined with proper bioassay methods.
Since the binding procedure of these biomolecules cannot be observed directly, markers capable of generating a detectable signal is used. In general, fluorescent material, radioactive material, enzyme or magnetic particle is used as the marker. In this detection method, it is important to generate a high sensitive signal so as to enable recognition of a trace amount of detection molecule.
In particular, target materials to be analyzed are recently diversified in the fields of development of new drug and diagnosis with development of synthetic chemistry and life science, and these target materials are very high in cost and are not easily obtained. Therefore, there is increasing needs for cost reduction through the trace analysis.
Among detection methods to ensure generation of high sensitive signal, various methods using magnetic particles have been reported.
Patent document 1 discloses a method in which recognition agents selectively immobilizing target molecules are bound to magnetizable particles and a magnetoresistive or magnetostrictive response of these bound particles to a magnetic field sensor is observed to detect the particles.
There has been developed a method of detecting a desired DNA by immobilizing a DNA to a Giant Magnetoresistive (GMR) device and measuring a magnetic flux of a magnetic particle, which is used as a marker, as a value of resistance variation. Also, there is a method, in which in order to find whether magnetic particles are immobilized by a biological recognition procedure, a residual magnetism and a magnetic susceptibility from a magnetic particle of iron oxide (Fe3O4) are measured from the magnetic particles using a Superconducting Quantum Interference Device (SQUID) to thereby recognize a detection molecule. The above described methods show high sensitive detection ability in biomolecule detection.
Those mentioned above are referred to as planar array types which immobilize receptor molecules on a planar substrate for analysis, with the externally-prepared sample. Additionally, since the biomolecules obtained in the above manner are those that are extracted from several thousands to several hundred and thousand cells and supplied, the characteristic of individual cells can hardly be known.
Although there exist apparatuses for separating biomolecules based on microbeads, they have limited ability to carry out complex operation since the microbeads are fabricated with a permanent magnet or an electromagnet of 5 mm or greater. Also, current technology for biomolecule translocation is not sufficient to control at nano-scale. Further, systems for bioassay are generally difficult in manufacture and high in cost, and also generate heat that may kill biological individuals. Furthermore, movement of magnetic media using this system is not smoother than the micro magnetic device for biomolecule translocation in accordance with the present invention.
In addition, since conventional magnetic tweezers and microneedles have only one tip, they can translocate only one magnetic medium and cannot translocate media in neighboring group.
Meanwhile, compared to the concepts like electric circuit and bubble microfluid, the concept of circuit, which can guide the digital flow of small packets of matter such as single cell and/or protein-coded colloidal particles, along patterned circuitry have not yet been demonstrated.
Patent document 2 discloses a microfluidic system comprising magnetic bead extracting device and a microfluid system including the same, adapted for the purpose of biomolecule separation and purification in the conventional microfluidic system. The microfluidic system selectively guides only the magnetic beads in the sample fluid flowing a passage of the sample fluid channel and collecting the same in the buffer solution chamber, and discharging the rest through the sample fluid outlet, thereby obtaining purified magnetic beads without having to perform separate washing process.
The inventors designed basic magnetophoretic circuit required to precisely control the flow of magnetic structures including magnetic beads and magnetic nanoparticles and magnetically-labelled single biomaterials along magnetically patterned circuitry.
The magnetic structures represent very flexible system for transporting and separating biological materials, and recent years have witnessed great progress in systems for controlling the movement of magnetic structures in micro scale. However, there have not been any demonstrations of the equivalent circuitry for controlling particle currents in fluids in a manner analogous to electronic circuits.
The inventors of the subject application discovered that matter currents defined above lithographically patterned magnetic tracks follow an equivalent form of Ohm's law, in which the driving frequency in this system plays the analogous role of voltage in electrical system. The inventors have also implemented more complex circuit elements, such as a matter rectifier, which transports matter only along preferred directions, and have used combinations of these fundamental circuit elements to demonstrate both focusing of magnetic structure to a magnetoresistive sensor, the storage capacitor and on demand release of single cells in localized apartments.
Transport of colloidal particles with magnetic micro-patterns exploits non-linear dynamic phenomena to precisely control the motion of magnetic structures in massively parallel.
The micro-pattern's periodic potential energy landscape is modulated by an external time-varying magnetic field to shift the regions of potential energy minima and transport magnetic structures along programmable pathways.
The inventors of the present application perceived the potential ability to control the movement of magnetic structures using changes in magnetic field and utilize the same, and completed the subject invention by developing a device for controlling transporting, trapping and escaping of biomaterials using micro magnetophoretic circuit and magnetic structures based on soft magnetic micro structures.